AIM: To determine the prevalence of SLC25A13 mutations in the Thai population.METHODS: A total of 1537 subjects representing the Thai population were screened for a novel pathologic allele p.Met1? (c.2T > C) and si...AIM: To determine the prevalence of SLC25A13 mutations in the Thai population.METHODS: A total of 1537 subjects representing the Thai population were screened for a novel pathologic allele p.Met1? (c.2T > C) and six previously known common SLC25A13 mutations: [I] (c.851_854delGTAT), [II] (g.IVS11 + 1G > A), [III] (c.1638_1660dup), [IV] (p.S225X), [V] (IVS13 + 1G > A), and [XIX] (g.IVS16ins3kb) using a newly developed TaqMan and established HybProbe assay, respectively. Sanger sequencing was employed for specimens showing an aberrant peak to confirm the targeted mutation as well as the unknown aberrant peaks detected. Frequencies of the mutations identified were compared in each region. Carrier frequency and disease prevalence of citrin deficiency caused by SCL25A13 mutations were estimated.RESULTS: p.Met1? was identified in the heterozygous state in 85 individuals, giving a carrier frequency of 1/18, which suggests possible selective advantage of this variant. The question of p.Met1? homozygote lethality remains unanswered which may serve as an explanation as to why this homozygote has yet to be identified in patients/controls even with high allele frequency. The p.Met1? mutation has rarely been studied in populations other than Thai and Chinese; therefore, may have been overlooked. Development of the TaqMan assay in the present study would allow a simple, rapid, and cost-effective method for mass screening. Heterozygous mutations: [XIX] and [I] were identified in 17 individuals, giving a carrier rate of 1/90 and a calculated homozygote rate of 1/33000. Two novel variants, g.IVS11 + 17C > G and c.1311C > T, of unknown clinical significance were identified at low frequency.CONCLUSION: This study highlighted the current underestimation of citrin deficiency and suggests the possible selective advantage of the p.Met1? allele.展开更多
BACKGROUND Expression of the full-length isoform of Abelson interactor 1(ABI1),ABI1-p65,is increased in colorectal carcinoma(CRC)and is thought to be involved in one or more steps leading to tumor progression or metas...BACKGROUND Expression of the full-length isoform of Abelson interactor 1(ABI1),ABI1-p65,is increased in colorectal carcinoma(CRC)and is thought to be involved in one or more steps leading to tumor progression or metastasis.The ABI1 splice isoform-L(ABI1-SiL)has conserved WAVE2-binding and SH3 domains,lacks the homeodomain homologous region,and is missing the majority of PxxP-and Pro-rich domains found in full-length ABI1-p65.Thus,ABI1-SiL domain structure suggests that the protein may regulate CRC cell morphology,adhesion,migration,and metastasis via interactions with the WAVE2 complex pathway.AIM To investigate the potential role and underlying mechanisms associated with ABI1-SiL-mediated regulation of CRC.METHODS ABI1-SiL mRNA expression in CC tissue and cell lines was measured using both qualitative reverse transcriptase-polymerase chain reaction(RT-PCR)and realtime quantitative RT-PCR.A stably ABI1-SiL overexpressing SW480 cell model was constructed using Lipofectamine 2000,and cells selected with G418.Image J software,CCK8,and transwell assays were used to investigate SW480 cell surface area,proliferation,migration,and invasion.Immunoprecipitation,Western blot,and co-localization assays were performed to explore intermolecular interactions between ABI1-SiL,WAVE2,and ABI1-p65 proteins.RESULTS ABI1-SiL was expressed in normal colon tissue and was significantly decreased in CRC cell lines and tissues.Overexpression of ABI1-SiL in SW480 cells significantly increased the cell surface area and inhibited the adhesive and migration properties of the cells,but did not alter their invasive capacity.Similar to ABI1-p65,ABI1-SiL still binds WAVE2,and the ABI1-p65 isoform in SW480 cells.Furthermore,co-localization assays confirmed these intermolecular interactions.CONCLUSION These results support a model in which ABI1-SiL plays an anti-oncogenic role by competitively binding to WAVE2 and directly interacting with phosphorylated and non-phosphorylated ABI1-p65,functioning as a dominant-negative form of ABI1-p65.展开更多
Polypyrimidine tract-binding protein 1(PTBP1)plays an essential role in splicing and is expressed in almost all cell types in humans,unlike the other proteins of the PTBP family.PTBP1 mediates several cellular process...Polypyrimidine tract-binding protein 1(PTBP1)plays an essential role in splicing and is expressed in almost all cell types in humans,unlike the other proteins of the PTBP family.PTBP1 mediates several cellular processes in certain types of cells,including the growth and differentiation of neuronal cells and activation of immune cells.Its function is regulated by various molecules,including micro RNAs(mi RNAs),long non-coding RNAs(lnc RNAs),and RNA-binding proteins.PTBP1 plays roles in various diseases,particularly in some cancers,including colorectal cancer,renal cell cancer,breast cancer,and glioma.In cancers,it acts mainly as a regulator of glycolysis,apoptosis,proliferation,tumorigenesis,invasion,and migration.The role of PTBP1 in cancer has become a popular research topic in recent years,and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer.In this review,we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.展开更多
目的探讨前2肽前列腺特异性抗原(isoform[-2]prostate specific antigen,p2PSA)及前列腺健康指数(prostate health index,PHI)早期诊断前列腺癌的临床价值。方法选择2019年11月至2021年2月在昆明医科大学第二附属医院住院治疗并拟首次...目的探讨前2肽前列腺特异性抗原(isoform[-2]prostate specific antigen,p2PSA)及前列腺健康指数(prostate health index,PHI)早期诊断前列腺癌的临床价值。方法选择2019年11月至2021年2月在昆明医科大学第二附属医院住院治疗并拟首次接受经超声引导下前列腺穿刺活检或手术切除的103例患者,根据病理结果分为前列腺癌组(45例)与前列腺良性疾病组(以下简称良性疾病组,58例),选择同期健康体检的43例健康男性作为健康对照组,进行各项血清学指标检测。根据总前列腺特异性抗原(total prostate specific antigen,tPSA)检测结果将146例研究对象分为tPSA≤10ng/ml组与tPSA>10ng/ml组,每组再各分出前列腺癌亚组与非前列腺癌亚组。计算游离/总前列腺特异性抗原(free/total prostate specific antigen,f/tPSA)和PHI。比较各项指标差异,用受试者工作特征(receiver operating characteristic,ROC)曲线评价不同分组中各项指标诊断前列腺癌的效能。结果前列腺癌组血清tPSA、游离前列腺特异性抗原(free prostate specific antigen,fPSA)、p2PSA水平及PHI均明显高于良性疾病组及健康对照组,而f/tPSA则相反,差异均有显著性(P<0.05)。PHI的曲线下面积最大(0.89,0.95),提示其诊断效能最佳。结论PHI是一个敏感度、特异度均较高且不受tPSA水平局限的优秀指标,而p2PSA相比之下优势不明显。PHI有望成为前列腺癌早期诊断的最佳指标。展开更多
AIM: To investigate the expression of myeloid differentiation protein-2 (MD-2), MD-2B (a splicing isoform of MD-2 that can block Toll-like receptor 4 (TLR4)/MD-2 LPS-mediated signal transduction) and TLR4 in the liver...AIM: To investigate the expression of myeloid differentiation protein-2 (MD-2), MD-2B (a splicing isoform of MD-2 that can block Toll-like receptor 4 (TLR4)/MD-2 LPS-mediated signal transduction) and TLR4 in the liver of acute cholangitis rats. METHODS: Male Sprague-Dawley rats (SPF level) were randomly divided into four groups: (A) sham-operated group; (B) simple common bile duct ligation group; (C)acute cholangitis group; and (D) acute cholangitis anti- TLR4 intervention group (n = 25 per group). Rat liver tissue samples were used to detect TLR4, MD-2 and MD-2B mRNA expression by fluorescence quantitative PCR in parallel with pathological changes. RESULTS: In acute cholangitis, liver TLR4 and MD-2 mRNA expression levels at 6, 12, 24, 48 and 72 h were gradually up-regulated but MD-2B mRNA expression gradually down-regulated (P < 0.05). After TLR4 antibody treatment, TLR4 and MD-2 mRNA expression were lower compared with the acute cholangitis group (P < 0.05). However, MD-2B mRNA expression was higher than in the acute cholangitis group (P < 0.05). MD-2 and TLR4 mRNA expressions were positively correlated (r = 0.94981, P < 0.05) and MD-2B mRNA expression was negatively correlated with MD-2 and TLR4 mRNA (r = -0.89031, -0.88997, P< 0.05). CONCLUSION: In acute cholangitis, MD-2 plays an important role in the process of TLR4- mediated in? am- matory response to liver injury while MD-2B plays a negative regulatory role.展开更多
AIM:To analyze the risk of coronary heart disease in patients with type 2 diabetes mellitus(T2DM)receiving standard medical treatment.METHODS:We performed a retrospective chart analysis of 269 middle-aged patients(age...AIM:To analyze the risk of coronary heart disease in patients with type 2 diabetes mellitus(T2DM)receiving standard medical treatment.METHODS:We performed a retrospective chart analysis of 269 middle-aged patients(age 45-64 years,mean age,53.9±5.5 years)with T2DM and without atherosclerotic cardiovascular events who underwent typing to determine their apolipoprotein E(apoE)isoforms.The apoE isoforms were determined using isoelectric focusing,followed by immunoblotting.We retrospectively evaluated the charts of the 269 patients,recorded between their first visit to the hospital(the study's start point,between 1987 and 1992)and the occurrence of an atherosclerotic cardiovascular event(the study's endpoint)or January 2004,whichever came first.The age-adjusted mean values and the prevalences of covariates were calculated to compare the laboratory data among the apoE phenotypes.To investigate the association of risk factors with the incidence of coronary heart disease during the follow-up period,monovariate and multivariate Cox regression models were used.RESULTS:At enrollment,the mean serum low density lipoprotein(LDL)cholesterol levels were lowest(2.92± 0.89 mmol/L)among the subjects with apoE2(apoE2/2 or apoE2/3)and highest(3.52±0.77 mmol/L)among the subjects with apoE4(apoE3/4 or apoE4/4).No significant differences in mean age or the percentage of smokers were observed among the three groups.Furthermore,no significant differences were observed in the systolic and diastolic blood pressures,body mass index,HbA1c level or serum triglyceride levels among the three groups.There were 47 cases of coronary heart disease over 3285 person-years of follow-up.An age-adjusted multivariate Cox proportional model identified diabetic retinopathy(hazard ratio,2.38,95% CI:1.28-4.43,P=0.006),a high systolic blood pressure(hazard ratio,1.04,95%CI:1.02-1.06,P<0.001) and high HbA1c values(hazard ratio,1.19,95%CI:1.02-1.38,P=0.0029),but not the LDL cholesterol value at enrollment(hazard ratio,1.01,95%CI:0.97-1.05,P=0.77)nor the speci展开更多
先天性双侧输精管缺如(congenital bilateral absence of vas deferens,CBAVD)可导致梗阻性无精子症,是男性不育的常见病因之一。CBAVD致病有关的基因种类繁多,其致病机制各有特点,但又有一定的联系;同时鉴于CBAVD在不育症的比例,合适...先天性双侧输精管缺如(congenital bilateral absence of vas deferens,CBAVD)可导致梗阻性无精子症,是男性不育的常见病因之一。CBAVD致病有关的基因种类繁多,其致病机制各有特点,但又有一定的联系;同时鉴于CBAVD在不育症的比例,合适的临床诊治和遗传咨询显得尤为重要。本文就CBAVD的致病机制和临床诊疗进行综述,以期待为中国CBAVD患者的诊治和遗传咨询提供参考。展开更多
p53凋亡刺激蛋白2(apoptosis stimulating protein 2 of p53,ASPP2)能够与p53蛋白结合特异性地增强其促细胞凋亡功能,进而发挥肿瘤抑制作用.我们发现的1个比ASPP2少300多个N端氨基酸的异构体ΔASPP2.目前,ΔASPP2对p53起何种作用尚不清...p53凋亡刺激蛋白2(apoptosis stimulating protein 2 of p53,ASPP2)能够与p53蛋白结合特异性地增强其促细胞凋亡功能,进而发挥肿瘤抑制作用.我们发现的1个比ASPP2少300多个N端氨基酸的异构体ΔASPP2.目前,ΔASPP2对p53起何种作用尚不清楚.在本研究中,我们构建了rAd-ASPP2、rAd-ΔASPP2腺病毒,利用rAd-p53、rAd-ASPP2、rAd-ΔASPP2感染p53缺失的细胞系H1299,在MMS的作用下研究ASPP2和ΔASPP2对p53介导的细胞凋亡的影响.结果发现,p53自身过表达能明显促进肿瘤细胞的凋亡;ASPP2可显著增强p53介导的MMS引起的H1299细胞凋亡的作用;然而,ΔASPP2对p53介导的细胞凋亡没有明显影响但却显著抑制rAd-ASPP2增强的rAd-p53的促细胞凋亡作用.p53-ASPP2复合体可能改变p53蛋白的构象,促进p53和增强子Bax的结合活性.p53转录调控基因的表达研究显示,ΔASPP2的存在可显著抑制ASPP2增强p53介导的bax基因转录活性,提示ΔASPP2可能与ASPP2结合后来抑制p53的凋亡基因转录活性.展开更多
基金Supported by A joint grant from Mahidol University Faculty of Science and Ramathibodi Hospital Faculty of Medicine (Jensen LT and Wattanasirichaigoon D)Mahidol University (Wattanasirichaigoon D: 49/2556)+2 种基金the Pharmacogenomics Project,the collaborative project from the Thailand Center of Excellence for Life Science and Mahidol University to Sukasem Cthe Medical Scholars Program of Mahidol University (Wongkittichote P)a recipient (Wattanasirichaigoon D) of Research Career Development Award,Faculty of Medicine Ramathibodi Hospital
文摘AIM: To determine the prevalence of SLC25A13 mutations in the Thai population.METHODS: A total of 1537 subjects representing the Thai population were screened for a novel pathologic allele p.Met1? (c.2T > C) and six previously known common SLC25A13 mutations: [I] (c.851_854delGTAT), [II] (g.IVS11 + 1G > A), [III] (c.1638_1660dup), [IV] (p.S225X), [V] (IVS13 + 1G > A), and [XIX] (g.IVS16ins3kb) using a newly developed TaqMan and established HybProbe assay, respectively. Sanger sequencing was employed for specimens showing an aberrant peak to confirm the targeted mutation as well as the unknown aberrant peaks detected. Frequencies of the mutations identified were compared in each region. Carrier frequency and disease prevalence of citrin deficiency caused by SCL25A13 mutations were estimated.RESULTS: p.Met1? was identified in the heterozygous state in 85 individuals, giving a carrier frequency of 1/18, which suggests possible selective advantage of this variant. The question of p.Met1? homozygote lethality remains unanswered which may serve as an explanation as to why this homozygote has yet to be identified in patients/controls even with high allele frequency. The p.Met1? mutation has rarely been studied in populations other than Thai and Chinese; therefore, may have been overlooked. Development of the TaqMan assay in the present study would allow a simple, rapid, and cost-effective method for mass screening. Heterozygous mutations: [XIX] and [I] were identified in 17 individuals, giving a carrier rate of 1/90 and a calculated homozygote rate of 1/33000. Two novel variants, g.IVS11 + 17C > G and c.1311C > T, of unknown clinical significance were identified at low frequency.CONCLUSION: This study highlighted the current underestimation of citrin deficiency and suggests the possible selective advantage of the p.Met1? allele.
基金National Natural Science Foundation of China,No.30872923 and No.81672853and Peking University People’s Hospital Scientific Research Development Found,No.RDH2020-11.
文摘BACKGROUND Expression of the full-length isoform of Abelson interactor 1(ABI1),ABI1-p65,is increased in colorectal carcinoma(CRC)and is thought to be involved in one or more steps leading to tumor progression or metastasis.The ABI1 splice isoform-L(ABI1-SiL)has conserved WAVE2-binding and SH3 domains,lacks the homeodomain homologous region,and is missing the majority of PxxP-and Pro-rich domains found in full-length ABI1-p65.Thus,ABI1-SiL domain structure suggests that the protein may regulate CRC cell morphology,adhesion,migration,and metastasis via interactions with the WAVE2 complex pathway.AIM To investigate the potential role and underlying mechanisms associated with ABI1-SiL-mediated regulation of CRC.METHODS ABI1-SiL mRNA expression in CC tissue and cell lines was measured using both qualitative reverse transcriptase-polymerase chain reaction(RT-PCR)and realtime quantitative RT-PCR.A stably ABI1-SiL overexpressing SW480 cell model was constructed using Lipofectamine 2000,and cells selected with G418.Image J software,CCK8,and transwell assays were used to investigate SW480 cell surface area,proliferation,migration,and invasion.Immunoprecipitation,Western blot,and co-localization assays were performed to explore intermolecular interactions between ABI1-SiL,WAVE2,and ABI1-p65 proteins.RESULTS ABI1-SiL was expressed in normal colon tissue and was significantly decreased in CRC cell lines and tissues.Overexpression of ABI1-SiL in SW480 cells significantly increased the cell surface area and inhibited the adhesive and migration properties of the cells,but did not alter their invasive capacity.Similar to ABI1-p65,ABI1-SiL still binds WAVE2,and the ABI1-p65 isoform in SW480 cells.Furthermore,co-localization assays confirmed these intermolecular interactions.CONCLUSION These results support a model in which ABI1-SiL plays an anti-oncogenic role by competitively binding to WAVE2 and directly interacting with phosphorylated and non-phosphorylated ABI1-p65,functioning as a dominant-negative form of ABI1-p65.
基金Project supported by the National Natural Science Foundation of China(Nos.81773179,81272972,and 81472355)the Program for New Century Excellent Talents in University(No.NCET-10-0790)+2 种基金the Hunan Provincial Science and Technology Department(Nos.2016JC 2049 and 2014FJ6006)the Hunan Provincial Natural Science Foundation of China(No.2016JJ2172)the Undergraduate Training Programs for Innovation and Entrepreneurship(Nos.201810533368,GS201910533474,and GS201910533236),China.
文摘Polypyrimidine tract-binding protein 1(PTBP1)plays an essential role in splicing and is expressed in almost all cell types in humans,unlike the other proteins of the PTBP family.PTBP1 mediates several cellular processes in certain types of cells,including the growth and differentiation of neuronal cells and activation of immune cells.Its function is regulated by various molecules,including micro RNAs(mi RNAs),long non-coding RNAs(lnc RNAs),and RNA-binding proteins.PTBP1 plays roles in various diseases,particularly in some cancers,including colorectal cancer,renal cell cancer,breast cancer,and glioma.In cancers,it acts mainly as a regulator of glycolysis,apoptosis,proliferation,tumorigenesis,invasion,and migration.The role of PTBP1 in cancer has become a popular research topic in recent years,and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer.In this review,we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.
文摘目的探讨前2肽前列腺特异性抗原(isoform[-2]prostate specific antigen,p2PSA)及前列腺健康指数(prostate health index,PHI)早期诊断前列腺癌的临床价值。方法选择2019年11月至2021年2月在昆明医科大学第二附属医院住院治疗并拟首次接受经超声引导下前列腺穿刺活检或手术切除的103例患者,根据病理结果分为前列腺癌组(45例)与前列腺良性疾病组(以下简称良性疾病组,58例),选择同期健康体检的43例健康男性作为健康对照组,进行各项血清学指标检测。根据总前列腺特异性抗原(total prostate specific antigen,tPSA)检测结果将146例研究对象分为tPSA≤10ng/ml组与tPSA>10ng/ml组,每组再各分出前列腺癌亚组与非前列腺癌亚组。计算游离/总前列腺特异性抗原(free/total prostate specific antigen,f/tPSA)和PHI。比较各项指标差异,用受试者工作特征(receiver operating characteristic,ROC)曲线评价不同分组中各项指标诊断前列腺癌的效能。结果前列腺癌组血清tPSA、游离前列腺特异性抗原(free prostate specific antigen,fPSA)、p2PSA水平及PHI均明显高于良性疾病组及健康对照组,而f/tPSA则相反,差异均有显著性(P<0.05)。PHI的曲线下面积最大(0.89,0.95),提示其诊断效能最佳。结论PHI是一个敏感度、特异度均较高且不受tPSA水平局限的优秀指标,而p2PSA相比之下优势不明显。PHI有望成为前列腺癌早期诊断的最佳指标。
基金Supported by the Medical Technology Research Foundation of Guangdong Province, No. A2008475
文摘AIM: To investigate the expression of myeloid differentiation protein-2 (MD-2), MD-2B (a splicing isoform of MD-2 that can block Toll-like receptor 4 (TLR4)/MD-2 LPS-mediated signal transduction) and TLR4 in the liver of acute cholangitis rats. METHODS: Male Sprague-Dawley rats (SPF level) were randomly divided into four groups: (A) sham-operated group; (B) simple common bile duct ligation group; (C)acute cholangitis group; and (D) acute cholangitis anti- TLR4 intervention group (n = 25 per group). Rat liver tissue samples were used to detect TLR4, MD-2 and MD-2B mRNA expression by fluorescence quantitative PCR in parallel with pathological changes. RESULTS: In acute cholangitis, liver TLR4 and MD-2 mRNA expression levels at 6, 12, 24, 48 and 72 h were gradually up-regulated but MD-2B mRNA expression gradually down-regulated (P < 0.05). After TLR4 antibody treatment, TLR4 and MD-2 mRNA expression were lower compared with the acute cholangitis group (P < 0.05). However, MD-2B mRNA expression was higher than in the acute cholangitis group (P < 0.05). MD-2 and TLR4 mRNA expressions were positively correlated (r = 0.94981, P < 0.05) and MD-2B mRNA expression was negatively correlated with MD-2 and TLR4 mRNA (r = -0.89031, -0.88997, P< 0.05). CONCLUSION: In acute cholangitis, MD-2 plays an important role in the process of TLR4- mediated in? am- matory response to liver injury while MD-2B plays a negative regulatory role.
文摘AIM:To analyze the risk of coronary heart disease in patients with type 2 diabetes mellitus(T2DM)receiving standard medical treatment.METHODS:We performed a retrospective chart analysis of 269 middle-aged patients(age 45-64 years,mean age,53.9±5.5 years)with T2DM and without atherosclerotic cardiovascular events who underwent typing to determine their apolipoprotein E(apoE)isoforms.The apoE isoforms were determined using isoelectric focusing,followed by immunoblotting.We retrospectively evaluated the charts of the 269 patients,recorded between their first visit to the hospital(the study's start point,between 1987 and 1992)and the occurrence of an atherosclerotic cardiovascular event(the study's endpoint)or January 2004,whichever came first.The age-adjusted mean values and the prevalences of covariates were calculated to compare the laboratory data among the apoE phenotypes.To investigate the association of risk factors with the incidence of coronary heart disease during the follow-up period,monovariate and multivariate Cox regression models were used.RESULTS:At enrollment,the mean serum low density lipoprotein(LDL)cholesterol levels were lowest(2.92± 0.89 mmol/L)among the subjects with apoE2(apoE2/2 or apoE2/3)and highest(3.52±0.77 mmol/L)among the subjects with apoE4(apoE3/4 or apoE4/4).No significant differences in mean age or the percentage of smokers were observed among the three groups.Furthermore,no significant differences were observed in the systolic and diastolic blood pressures,body mass index,HbA1c level or serum triglyceride levels among the three groups.There were 47 cases of coronary heart disease over 3285 person-years of follow-up.An age-adjusted multivariate Cox proportional model identified diabetic retinopathy(hazard ratio,2.38,95% CI:1.28-4.43,P=0.006),a high systolic blood pressure(hazard ratio,1.04,95%CI:1.02-1.06,P<0.001) and high HbA1c values(hazard ratio,1.19,95%CI:1.02-1.38,P=0.0029),but not the LDL cholesterol value at enrollment(hazard ratio,1.01,95%CI:0.97-1.05,P=0.77)nor the speci
文摘先天性双侧输精管缺如(congenital bilateral absence of vas deferens,CBAVD)可导致梗阻性无精子症,是男性不育的常见病因之一。CBAVD致病有关的基因种类繁多,其致病机制各有特点,但又有一定的联系;同时鉴于CBAVD在不育症的比例,合适的临床诊治和遗传咨询显得尤为重要。本文就CBAVD的致病机制和临床诊疗进行综述,以期待为中国CBAVD患者的诊治和遗传咨询提供参考。
文摘p53凋亡刺激蛋白2(apoptosis stimulating protein 2 of p53,ASPP2)能够与p53蛋白结合特异性地增强其促细胞凋亡功能,进而发挥肿瘤抑制作用.我们发现的1个比ASPP2少300多个N端氨基酸的异构体ΔASPP2.目前,ΔASPP2对p53起何种作用尚不清楚.在本研究中,我们构建了rAd-ASPP2、rAd-ΔASPP2腺病毒,利用rAd-p53、rAd-ASPP2、rAd-ΔASPP2感染p53缺失的细胞系H1299,在MMS的作用下研究ASPP2和ΔASPP2对p53介导的细胞凋亡的影响.结果发现,p53自身过表达能明显促进肿瘤细胞的凋亡;ASPP2可显著增强p53介导的MMS引起的H1299细胞凋亡的作用;然而,ΔASPP2对p53介导的细胞凋亡没有明显影响但却显著抑制rAd-ASPP2增强的rAd-p53的促细胞凋亡作用.p53-ASPP2复合体可能改变p53蛋白的构象,促进p53和增强子Bax的结合活性.p53转录调控基因的表达研究显示,ΔASPP2的存在可显著抑制ASPP2增强p53介导的bax基因转录活性,提示ΔASPP2可能与ASPP2结合后来抑制p53的凋亡基因转录活性.
